SARS-CoV-2-specific T cells associate with inflammation and reduced lung function in pulmonary post-acute sequalae of SARS-CoV-2.

As of January 2022, at least 60 million individuals are estimated to develop post-acute sequelae of SARS-CoV-2 (PASC) after infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). While elevated levels of SARS-CoV-2-specific T cells have been observed in non-specific PASC, little is known about their impact on pulmonary function which is compromised in the majority of these individuals. This study compares frequencies of SARS-CoV-2-specific T cells and inflammatory markers with lung function in participants with pulmonary PASC and resolved COVID-19 (RC). Compared to RC, participants with respiratory PASC had between 6- and 105-fold higher frequencies of IFN-γ- and TNF-α-producing SARS-CoV-2-specific CD4+ and CD8+ T cells in peripheral blood, and elevated levels of plasma CRP and IL-6. Importantly, in PASC participants the frequency of TNF-α-producing SARS-CoV-2-specific CD4+ and CD8+ T cells, which exhibited the highest levels of Ki67 indicating they were activity dividing, correlated positively with plasma IL-6 and negatively with measures of lung function, including forced expiratory volume in one second (FEV1), while increased frequencies of IFN-γ-producing SARS-CoV-2-specific T cells associated with prolonged dyspnea. Statistical analyses stratified by age, number of comorbidities and hospitalization status demonstrated that none of these factors affect differences in the frequency of SARS-CoV-2 T cells and plasma IL-6 levels measured between PASC and RC cohorts. Taken together, these findings demonstrate elevated frequencies of SARS-CoV-2-specific T cells in individuals with pulmonary PASC are associated with increased systemic inflammation and decreased lung function, suggesting that SARS-CoV-2-specific T cells contribute to lingering pulmonary symptoms. These findings also provide mechanistic insight on the pathophysiology of PASC that can inform development of potential treatments to reduce symptom burden.

Association between monoclonal antibody therapy, vaccination, and longer-term symptom resolution after acute COVID-19.

Effective therapies for reducing post-acute sequelae of COVID-19 (PASC) symptoms are lacking. Evaluate the association between monoclonal antibody (mAb) treatment or COVID-19 vaccination with symptom recovery in COVID-19 participants. The longitudinal survey-based cohort study was conducted from April 2021 to January 2022 across a multihospital Colorado health system. Adults ≥18 years with a positive SARS-CoV-2 test were included. Primary exposures were mAb treatment and COVID-19 vaccination. The primary outcome was time to symptom resolution after SARS-CoV-2 positive test date. The secondary outcome was hospitalization within 28 days of a positive SARS-CoV-2 test. Analysis included 1612 participants, 539 mAb treated, and 486 with ≥2 vaccinations. Time to symptom resolution was similar between mAb treated versus untreated patients (adjusted hazard ratio (aHR): 0.90, 95% CI: 0.77-1.04). Time to symptom resolution was shorter for patients who received ≥2 vaccinations compared to those unvaccinated (aHR: 1.56, 95% CI: 1.31-1.88). 28-day hospitalization risk was lower for patients receiving mAb therapy (adjusted odds ratio [aOR]: 0.31, 95% CI: 0.19-0.50) and ≥2 vaccinations (aOR: 0.33, 95% CI: 0.20-0.55), compared with untreated or unvaccinated status. Analysis included 1612 participants, 539 mAb treated, and 486 with ≥2 vaccinations. Time to symptom resolution was similar between mAb treated versus untreated patients (adjusted hazard ratio (aHR): 0.90, 95% CI: 0.77-1.04). Time to symptom resolution was shorter for patients who received ≥2 vaccinations compared to those unvaccinated (aHR: 1.56, 95% CI: 1.31-1.88). 28-day hospitalization risk was lower for patients receiving mAb therapy (adjusted odds ratio [aOR]: 0.31, 95% CI: 0.19-0.50) and ≥2 vaccinations (aOR: 0.33, 95% CI: 0.20-0.55), compared with untreated or unvaccinated status. COVID-19 vaccination, but not mAb therapy, was associated with a shorter time to symptom resolution. Both were associated with lower 28-day hospitalization.

Sounding the Alarm: What Clinicians Need to Know about Physical, Emotional, and Cognitive Recovery After Venoarterial Extracorporeal Membrane Oxygenation.

OBJECTIVE: We summarize the existing data on the occurrence of physical, emotional, and cognitive dysfunction associated with postintensive care syndrome (PICS) in adult survivors of venoarterial extracorporeal membrane oxygenation (VA-ECMO). DATA SOURCES: MEDLINE, Cochrane Library, EMBASE, Web of Science, and CINAHL databases were searched. STUDY SELECTION: Peer-reviewed studies of adults receiving VA-ECMO for any reason with at least one measure of health-related quality of life outcomes or PICS at long-term follow-up of at least 6 months were included. DATA EXTRACTION: The participant demographics and baseline characteristics, in-hospital outcomes, long-term health outcomes, quality of life outcome measures, and prevalence of PICS were extracted. DATA SYNTHESIS: Twenty-seven studies met inclusion criteria encompassing 3,271 patients who were treated with VA-ECMO. The studies were limited to single- or two-center studies. Outcomes variables and follow-up time points evaluated were widely heterogeneous which limits comprehensive analysis of PICS after VA-ECMO. In general, the longer-term PICS-related outcomes of survivors of VA-ECMO were worse than the general population, and approaching that of patients with chronic disease. Available studies identified high rates of abnormal 6-minute walk distance, depression, anxiety, and posttraumatic stress disorder that persisted for years. Half or fewer survivors return to work years after discharge. Only 2 of 27 studies examined cognitive outcomes and no studies evaluated cognitive dysfunction within the first year of recovery. No studies evaluated the impact of targeted interventions on these outcomes. CONCLUSIONS: Survivors of VA-ECMO represent a population of critically ill patients at high risk for deficits in physical, emotional, and cognitive function related to PICS. This systematic review highlights the alarming reality that PICS and in particular, neurocognitive outcomes, in survivors of VA-ECMO are understudied, underrecognized, and thus likely undertreated. These results underscore the imperative that we look beyond survival to focus on understanding the burden of survivorship with the goal of optimizing recovery and outcomes after these life-saving interventions. Future prospective, multicenter, longitudinal studies in recovery after VA-ECMO are justified.

Development of a Definition of Postacute Sequelae of SARS-CoV-2 Infection.

Importance: SARS-CoV-2 infection is associated with persistent, relapsing, or new symptoms or other health effects occurring after acute infection, termed postacute sequelae of SARS-CoV-2 infection (PASC), also known as long COVID. Characterizing PASC requires analysis of prospectively and uniformly collected data from diverse uninfected and infected individuals. Objective: To develop a definition of PASC using self-reported symptoms and describe PASC frequencies across cohorts, vaccination status, and number of infections. Design, Setting, and Participants: Prospective observational cohort study of adults with and without SARS-CoV-2 infection at 85 enrolling sites (hospitals, health centers, community organizations) located in 33 states plus Washington, DC, and Puerto Rico. Participants who were enrolled in the RECOVER adult cohort before April 10, 2023, completed a symptom survey 6 months or more after acute symptom onset or test date. Selection included population-based, volunteer, and convenience sampling. Exposure: SARS-CoV-2 infection. Main Outcomes and Measures: PASC and 44 participant-reported symptoms (with severity thresholds). Results: A total of 9764 participants (89% SARS-CoV-2 infected; 71% female; 16% Hispanic/Latino; 15% non-Hispanic Black; median age, 47 years [IQR, 35-60]) met selection criteria. Adjusted odds ratios were 1.5 or greater (infected vs uninfected participants) for 37 symptoms. Symptoms contributing to PASC score included postexertional malaise, fatigue, brain fog, dizziness, gastrointestinal symptoms, palpitations, changes in sexual desire or capacity, loss of or change in smell or taste, thirst, chronic cough, chest pain, and abnormal movements. Among 2231 participants first infected on or after December 1, 2021, and enrolled within 30 days of infection, 224 (10% [95% CI, 8.8%-11%]) were PASC positive at 6 months. Conclusions and Relevance: A definition of PASC was developed based on symptoms in a prospective cohort study. As a first step to providing a framework for other investigations, iterative refinement that further incorporates other clinical features is needed to support actionable definitions of PASC.

Medication prescribing for alcohol use disorders during alcohol-related encounters in a Colorado regional healthcare system.

RATIONALE: Investigations show that medications for alcohol use disorders (MAUD) reduce heavy drinking and relapses. However, only 1.6% of individuals with alcohol use disorders (AUD) receive MAUD across care settings. The epidemiology of MAUD prescribing in the acute care setting is incompletely described. We hypothesized that MAUD would be under prescribed in inpatient acute care hospital settings compared to the outpatient, emergency department (ED), and inpatient substance use treatment settings. METHODS: We evaluated electronic health record (EHR) data from adult patients with an International Classification of Diseases, 10th revision (ICD-10) alcohol-related diagnosis in the University of Colorado Health (UCHealth) system between January 1, 2016 and 31 December, 2019. Data from patients with an ICD-10 diagnosis code for opioid use disorder and those receiving MAUD prior to their first alcohol-related episode were excluded. The primary outcome was prescribing of MAUD, defined by prescription of naltrexone, acamprosate, and/or disulfiram. We performed bivariate and multivariate analyses to identify independent predictors of MAUD prescribing at UCHealth. RESULTS: We identified 48,421 unique patients with 136,205 alcohol-related encounters at UCHealth. Encounters occurred in the ED (42%), inpatient acute care (17%), inpatient substance use treatment (18%), or outpatient primary care (12%) settings. Only 2270 (5%) patients received MAUD across all settings. Female sex and addiction medicine consults positively predicted MAUD prescribing. In contrast, encounters outside inpatient substance use treatment, Hispanic ethnicity, and black or non-white race were negative predictors of MAUD prescribing. Compared to inpatient substance use treatment, inpatient acute care hospitalizations for AUD was associated with a 93% reduced odds of receiving MAUD. CONCLUSIONS: AUD-related ED and inpatient acute care hospital encounters in our healthcare system were common. Nevertheless, prescriptions for MAUD were infrequent in this population, particularly in inpatient settings. Our findings suggest that the initiation of MAUD for patients with alcohol-related diagnoses in acute care settings deserves additional evaluation.

Research Needs for Inpatient Management of Severe Alcohol Withdrawal Syndrome: An Official American Thoracic Society Research Statement.

Background: Severe alcohol withdrawal syndrome (SAWS) is highly morbid, costly, and common among hospitalized patients, yet minimal evidence exists to guide inpatient management. Research needs in this field are broad, spanning the translational science spectrum. Goals: This research statement aims to describe what is known about SAWS, identify knowledge gaps, and offer recommendations for research in each domain of the Institute of Medicine T0-T4 continuum to advance the care of hospitalized patients who experience SAWS. Methods: Clinicians and researchers with unique and complementary expertise in basic, clinical, and implementation research related to unhealthy alcohol consumption and alcohol withdrawal were invited to participate in a workshop at the American Thoracic Society 2019 International Conference. The committee was subdivided into four groups on the basis of interest and expertise: T0-T1 (basic science research with translation to humans), T2 (research translating to patients), T3 (research translating to clinical practice), and T4 (research translating to communities). A medical librarian conducted a pragmatic literature search to facilitate this work, and committee members reviewed and supplemented the resulting evidence, identifying key knowledge gaps. Results: The committee identified several investigative opportunities to advance the care of patients with SAWS in each domain of the translational science spectrum. Major themes included 1) the need to investigate non-γ-aminobutyric acid pathways for alcohol withdrawal syndrome treatment; 2) harnessing retrospective and electronic health record data to identify risk factors and create objective severity scoring systems, particularly for acutely ill patients with SAWS; 3) the need for more robust comparative-effectiveness data to identify optimal SAWS treatment strategies; and 4) recommendations to accelerate implementation of effective treatments into practice. Conclusions: The dearth of evidence supporting management decisions for hospitalized patients with SAWS, many of whom require critical care, represents both a call to action and an opportunity for the American Thoracic Society and larger scientific communities to improve care for a vulnerable patient population. This report highlights basic, clinical, and implementation research that diverse experts agree will have the greatest impact on improving care for hospitalized patients with SAWS.

Prospective telehealth analysis of functional performance, frailty, quality of life, and mental health after COVID-19 hospitalization.

BACKGROUND: COVID-19 is a global pandemic with poorly understood long-term consequences. Determining the trajectory of recovery following COVID-19 hospitalization is critical for prioritizing care, allocating resources, facilitating prognosis, and informing rehabilitation. The purpose of this study was to prospectively evaluate recovery following COVID-19 hospitalization. METHODS: Participants age 18 years or older who were hospitalized for ≥24 h due to COVID-19 completed phone/video call virtual assessments (including the 10-time chair rise test) and survey forms at three time points (2-6, 12, and 18 weeks) after hospital discharge. Univariate logistic and linear regression models assessed the associations of the outcomes with primary predictors (categorical age, sex, race/ethnicity group, and categorical pre-hospitalization frailty) at baseline; the same were used to assess differences in change from week 2-6 (continuous outcomes) or outcome persistence/worsening (categorical) at last contact. RESULTS: One hundred nine adults (age 53.0 [standard deviation 13.1]; 53% female) participated including 43 (39%) age 60 or greater; 59% identified as an ethnic and/or racial minority. Over 18 weeks, the mean time to complete the 10-time chair rise test decreased (i.e., improved) by 6.0 s (95% CI: 4.1, 7.9 s; p < 0.001); this change did not differ by pre-hospital frailty, race/ethnicity group, or sex, but those age ≥ 60 had greater improvement. At weeks 2-6, 67% of participants reported a worse Clinical Frailty Scale category compared to their pre-hospitalization level, whereas 42% reported a worse frailty score at 18 weeks. Participants who did not return to pre-hospitalization levels were more likely to be female, younger, and report a pre-hospitalization category of 'very fit' or 'well'. CONCLUSIONS: We found that functional performance improved from weeks 2-6 to 18 weeks of follow-up; that incident clinical frailty developed in some individuals following COVID-19; and that age, sex, race/ethnicity, and pre-hospitalization frailty status may impact recovery from COVID-19. Notably, individuals age 60 and older were more likely than those under age 45 years to return to their pre-hospitalization status and to make greater improvements in functional performance. The results of the present study provide insight into the trajectory of recovery among a representative cohort of individuals hospitalized due to COVID-19.

Care erosion in sedation assessment: A prospective comparison of usual care Richmond Agitation-Sedation Scale assessment with protocolized assessment for medical intensive care unit patients.

OBJECTIVES: To determine concordance between an explicit protocolized assessment of the Richmond Agitation-Sedation Scale and an assessment performed during usual care nursing practice. RESEARCH DESIGN: In an urban, safety-net hospital, intensive care nurses previously trained in sedation assessment recorded a bedside Richmond Agitation-Sedation Scale assessment, while study investigators used an explicit script to perform the assessment at a similar time point. Kappa indices determined concordance of the assessments. Bivariate analyses explored factors associated with discordance and unresponsiveness. RESULTS: Twenty-one subjects with 38 observations were analysed. Bedside nursing assessment was poorly concordant with protocolized assessment (ƙ = 0.21) with the former reporting significantly lighter sedation (median -2 vs. -5, p = .01). Bedside assessment was significantly less likely than protocolized assessment to categorize subjects as unresponsive (29 vs. 50%, p = .02). CONCLUSION: Methods used in usual clinical practice to assess adequacy of sedation frequently led to oversedation. We propose that care erosion, the deterioration of skills over time, may help explain this finding. IMPLICATIONS FOR NURSING MANAGEMENT: Results suggest sedation assessment may be particularly vulnerable to care erosion. Nurse managers should monitor for signs of care erosion and consider utilization of explicit scripts during sedation assessment and/or frequent education to ensure sedation assessment accuracy.

Discharge Destination As a Marker of Mobility Impairment in Survivors of Acute Respiratory Distress Syndrome.

OBJECTIVES: Discharge destination is a commonly used surrogate for long-term recovery in rehabilitation studies. We determined the accuracy of discharge destination as a surrogate marker for 6-month mobility impairment in acute respiratory distress syndrome survivors. DESIGN/SETTING: Secondary analysis of the Economic Analysis of Pulmonary Artery Catheters study, a long-term observational sub-study of the National Institutes of Health/National Heart, Lung, and Blood Institute Acute Respiratory Distress Syndrome Network Fluid and Catheter Treatment Trial. PATIENTS: Patients underwent functional assessment using the Health Utilities Index-2 mobility domains at 6 months. A score greater than or equal to 3 (i.e., need for assistive device) defined mobility impairment. Discharge to any institutional care constituted a care facility discharge. We used logistic regression to explore the association between discharge destination and mobility impairment. We generated test characteristics and receiver operating characteristics to assess the accuracy of discharge destination as a surrogate for mobility impairment. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A total of 591 patients were enrolled in Economic Analysis of Pulmonary Artery Catheters in whom 328 had functional measurements at 6 months with 116 (35%) of these patients discharged to a care facility. Care facility patients were older (mean age 53 vs 44 yr; p < 0.001) and had longer hospital durations (length of stay 29 vs 17 d; p < 0.001). Care facility discharge was associated with greater 6-month mobility impairment. Sensitivity and specificity of discharge to a care facility for mobility impairment were 40.5% (95% CI, 32.0-49.6%) and 79.3% (95% CI, 73.3-84.2%) at 6 months. Discharge destination alone was a poor discriminator of long-term mobility impairment (receiver operating characteristic area under the curve: 0.61 at 6 mo). CONCLUSIONS: Discharge to a care facility was strongly associated with mobility impairment 6 months after acute respiratory distress syndrome but discharge destination alone performed poorly as a surrogate for mobility impairment.

Substance use is independently associated with pneumonia severity in persons living with the human immunodeficiency virus (HIV).

Background: Pneumonia is common in persons living with the human immunodeficiency virus (HIV) (PLWH). Alcohol, cocaine, and marijuana impact pneumonia pathogenesis. We hypothesized that substance use was independently associated with pneumonia severity in PLWH and modified the effect of alcohol on pneumonia severity. Methods: Retrospective data analysis of PLWH admitted with a diagnosis of pneumonia was conducted. Alcohol use disorder was defined by the Alcohol Use Disorders Identification Test score ≥14. Drug use was quantified by self-report. Pneumonia severity was defined by the pneumonia severity index (PSI). Multivariable linear regression was used to test independent associations with pneumonia severity and effect modification by sex. Results: Of 196 PLWH, the mean age was 44 (SD = 9) years and the majority were men (71%). Ten percent (n = 19) of subjects met criteria for an alcohol use disorder (AUD). In subjects reporting alcohol use, 25% reported concomitant crack/cocaine use and 16% reported marijuana use. PSI scores were higher with lifetime use of crack/cocaine (mean PSI: 63.1 vs. 57.3, P = .06) and/or injection drug use (68.4 vs. 54.9, P = .04). PSI scores were lower with active marijuana use (51.5 vs. 62.2, P = .01). There was no significant difference in clinical outcomes. Sex modified the effect of drug use on PSI, with greater PSI scores in women with an AUD (ß = 58.1, 95% confidence interval [CI]: 46.7 to 69.5, P < .01), whereas active marijuana use mitigated the effect of AUD on PSI in men (ß = -12.7, 95% CI: -18.8 to -6.6, P < .01). Conclusions: Active alcohol and/or crack/cocaine use was associated with increased pneumonia severity in PLWH, with less severe pneumonia with marijuana use. Alcohol and marijuana effects on pneumonia severity differed by sex, with increased PSI in women and decreased PSI in men with concomitant marijuana and AUD.

Presence of an Alcohol Use Disorder is Associated with Greater Pneumonia Severity in Hospitalized HIV-Infected Patients.

PURPOSE: Pneumonia is common and more severe in human immunodeficiency virus (HIV)-infected patients. Alcohol consumption in pneumonia patients without HIV is associated with excess mortality and morbidity. However, studies are lacking on the impact of alcohol on pneumonia and HIV. Our goal was to determine if alcohol use was an independent risk factor for pneumonia severity in HIV-infected patients. METHODS: Secondary analysis of prospective cohort study data evaluating early bronchoscopy for pneumonia diagnosis in HIV patients between 2007 and 2011 was conducted. We defined AUDs using an alcohol use disorder identification test (AUDIT) score as follows: ≥8 indicates hazardous drinking and ≥14 indicates dependence. We quantified pneumonia severity using the pneumonia severity index (PSI). Multivariable linear regression was used to investigate the independent association between alcohol and pneumonia severity. RESULTS: A total of 196 HIV+ individuals comprised our cohort. Most cohort subjects were middle-aged African American men. Most subjects (70 %) reported not taking antiretroviral therapy. The overall prevalence of hazardous drinking was 24 % in our cohort (48/196) with 10 % (19/196) meeting the criteria for alcohol dependence. Alcohol consumption was significantly associated with pneumonia severity (r = 0.25, p < 0.001). Hazardous drinking (ß-coefficient 10.12, 95 % CI 2.95-17.29, p = 0.006) and alcohol dependence (ß-coefficient 12.89, 95 % CI 2.59-23.18, p = 0.014) were independent risk factors for pneumonia severity. Reported homelessness and men who have sex with men (MSM) status remained independent risk factors for more severe pneumonia after adjustment for the effects of alcohol. CONCLUSIONS: In a cohort of HIV patients with pneumonia, presence of an AUD was an independent risk factor for pneumonia severity. Homelessness and MSM status were associated with greater pneumonia severity in AUD patients.

Medical intensive care unit clinician attitudes and perceived barriers towards early mobilization of critically ill patients: a cross-sectional survey study.

BACKGROUND: Early mobilization (EM) of patients on mechanical ventilation (MV) is shown to improve outcomes after critical illness. Little is known regarding clinician knowledge of EM or multi-disciplinary barriers to use of EM in the intensive care unit (ICU). The goal of this study was to assess clinician knowledge regarding EM and identify barriers to its provision. METHODS: Simultaneous cross-sectional surveys of medical ICU (MICU) nurses (RN)/physical therapists (PT) respondents and physician (MD) respondents in a single MICU at an academic hospital in Seattle, WA in 2010-2011. Responses were indicated on a 5 point Likert scale and reported as proportion of respondents agreeing or disagreeing. Chi-square testing and Fisher's exact testing was performed to determine whether responses differed by duration of employment or prior EM experience. RESULTS: A total of 120 clinicians responded to the survey (91 MDs (response rate 82% (91/111)), 17 RNs (response rate 22%, (17/78)), and 12 PTs (response rate 86%, (12/14)), overall response rate 86%). Most clinicians indicated knowledge regarding benefits of EM. More attending physicians reported knowledge of EM benefits, but also that risks of EM outweigh the benefits compared to trainees (p = 0.02 and 0.01). Clinicians across disciplines reported near universal agreement to use of EM for patients on MV, while the minority reported agreement to EM for patients on vasoactive agents. The most frequently reported cross-disciplinary barriers to EM were staffing and time. Risk of self-injury and excess work stress were indicated as barriers by RN and PT respondents. CONCLUSIONS: MICU clinicians, at our institution, reported knowledge of EM in the ICU. Staffing and clinician time were frequently identified cross-disciplinary barriers. Risk of self-injury and excess work stress were frequently reported RN and PT barriers.

Prevalence of Alcohol Use Characterized by Phosphatidylethanol in Patients With Respiratory Failure Before and During the COVID-19 Pandemic.

BACKGROUND: Alcohol misuse is overlooked frequently in hospitalized patients, but is common among patients with pneumonia and acute hypoxic respiratory failure. Investigations in hospitalized patients rely heavily on self-report surveys or chart abstraction, which lack sensitivity. Therefore, our understanding of the prevalence of alcohol misuse before and during the COVID-19 pandemic is limited. RESEARCH QUESTION: In critically ill patients with respiratory failure, did the proportion of patients with alcohol misuse, defined by the direct biomarker phosphatidylethanol, vary over a period including the COVID-19 pandemic? STUDY DESIGN AND METHODS: Patients with acute hypoxic respiratory failure receiving mechanical ventilation were enrolled prospectively from 2015 through 2019 (before the pandemic) and from 2020 through 2022 (during the pandemic). Alcohol use data, including Alcohol Use Disorders Identification Test (AUDIT)-C scores, were collected from electronic health records, and phosphatidylethanol presence was assessed at ICU admission. The relationship between clinical variables and phosphatidylethanol values was examined using multivariable ordinal regression. Dichotomized phosphatidylethanol values (≥ 25 ng/mL) defining alcohol misuse were compared with AUDIT-C scores signifying misuse before and during the pandemic, and correlations between log-transformed phosphatidylethanol levels and AUDIT-C scores were evaluated and compared by era. Multiple imputation by chained equations was used to handle missing phosphatidylethanol data. RESULTS: Compared with patients enrolled before the pandemic (n = 144), patients in the pandemic cohort (n = 92) included a substantially higher proportion with phosphatidylethanol-defined alcohol misuse (38% vs 90%; P < .001). In adjusted models, absence of diabetes, positive results for COVID-19, and enrollment during the pandemic each were associated with higher phosphatidylethanol values. The correlation between health care worker-recorded AUDIT-C score and phosphatidylethanol level was significantly lower during the pandemic. INTERPRETATION: The higher prevalence of phosphatidylethanol-defined alcohol misuse during the pandemic suggests that alcohol consumption increased during this period, identifying alcohol misuse as a potential risk factor for severe COVID-19-associated respiratory failure. Results also suggest that AUDIT-C score may be less useful in characterizing alcohol consumption during high clinical capacity.

An Exploratory Analysis of Sociodemographic Factors Associated With Physical Functional Impairment in ICU Survivors.

IMPORTANCE: Physical functional impairment is one of three components of postintensive care syndrome (PICS) that affects up to 60% of ICU survivors. OBJECTIVES: To explore the prevalence of objective physical functional impairment among a diverse cohort of ICU survivors, both at discharge and longitudinally, and to highlight sociodemographic factors that might be associated with the presence of objective physical functional impairment. DESIGN, SETTING, AND PARTICIPANTS: This was a secondary analysis of 37 patients admitted to the ICU in New Orleans, Louisiana, and Denver, Colorado between 2016 and 2019 who survived with longitudinal follow-up data. MAIN OUTCOMES AND MEASURES: Our primary outcome of physical functional impairment was defined by handgrip strength and the short physical performance battery. We explored associations between functional impairment and sociodemographic factors that included race/ethnicity, sex, primary language, education status, and medical comorbidities. RESULTS: More than 75% of ICU survivors were affected by physical functional impairment at discharge and longitudinally at 3- to 6-month follow-up. We did not see a significant difference in the proportion of patients with physical functional impairment by race/ethnicity, primary language, or education status. Impairment was relatively higher in the follow-up period among women, compared with men, and those with comorbidities. Among 18 patients with scores at both time points, White patients demonstrated greater change in handgrip strength than non-White patients. Four non-White patients demonstrated diminished handgrip strength between discharge and follow-up. CONCLUSIONS AND RELEVANCE: In this exploratory analysis, we saw that the prevalence of objective physical functional impairment among ICU survivors was high and persisted after hospital discharge. Our findings suggest a possible relationship between race/ethnicity and physical functional impairment. These exploratory findings may inform future investigations to evaluate the impact of sociodemographic factors on functional recovery.

Impact of Alcohol Misuse on Requirements for Critical Care Services and Development of Hospital Delirium in Patients With COVID-19 pneumonia.

Alcohol misuse has been associated with increased morbidity in the setting of pulmonary infections, including the need for critical care resource utilization and development of delirium. How alcohol misuse impacts morbidity and outcomes among patients admitted with COVID-19 pneumonia is not well described. We sought to determine if alcohol misuse was associated with an increased need for critical care resources and development of delirium among patients hospitalized with COVID-19 pneumonia. DESIGN: Retrospective cohort study. SETTING: Twelve University of Colorado hospitals between March 2020 and April 2021. PATIENTS: Adults with a COVID-19 diagnosis. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The primary outcome was admission to the ICU. Secondary outcomes included need for mechanical ventilation, development of delirium, and in-hospital mortality. Alcohol misuse was defined by International Classification of Diseases, 10th Revision codes. Of 5,979 patients hospitalized with COVID-19, 26% required ICU admission and 15.4% required mechanical ventilation. Delirium developed in 4.5% and 10.5% died during hospitalization. Alcohol misuse was identified in 4%. In analyses adjusted for age, sex, body mass index, diabetes, and liver disease, alcohol misuse was associated with increased odds of ICU admission (adjusted odds ratio [aOR], 1.46; p < 0.01), mechanical ventilation (aOR, 1.43; p = 0.03), and delirium (aOR, 5.55; p < 0.01) compared with patients without misuse. Mortality rates were not associated with alcohol misuse alone, although the presence of both alcohol misuse and in-hospital delirium significantly increased odds of in-hospital death (aOR, 2.60; p = 0.04). CONCLUSIONS: Among patients hospitalized with COVID-19, alcohol misuse was associated with increased utilization of critical care resources including ICU admission and mechanical ventilation. Delirium was an important modifiable risk factor associated with worse outcomes in hospitalized patients with alcohol misuse, including increased odds of death.

Predictors of adverse outcomes in aged patients critically ill with COVID-19: a retrospective study.

Older patients represent an inordinate proportion of intensive care unit (ICU) admissions and ICU mortality associated with coronavirus disease 2019 (COVID-19). In this retrospective cohort study, we examine 198 patients, aged 18 years or older, admitted to the ICU from March to June 2020. We aim to understand the relationships between age, number of comorbidities, and independent living prior to admission on outcomes of mortality, length of stay, renal failure, respiratory failure, and shock. In this cohort, we find that overall mortality was associated with respiratory failure severity (for every decrease of P:F by 50, odds ratio (OR) 2.98 (1.65-6.08)), acute renal failure (OR 4.61 (1.2-19.7)), and age 65 or greater (OR: 3.7 (1.86-7.36)). Surprisingly, increasing age was associated with less severe respiratory failure (R = 0.22, p < 0.01). When adjusting for pre-existing chronic kidney disease, age was not associated with development of acute kidney injury (OR: 1.01 (0.99-1.03)). While chronologic age is associated with mortality, it is not associated independently with severe end organ damage. This is consistent with growing evidence suggesting that a complex interplay between multimorbidity, immunosenescence, and physiologic age is primarily responsible for the vulnerability to COVID-19.

Using Wearable Technology to Quantify Physical Activity Recovery: Secondary Report From the AFTER (App-Facilitated Tele-Rehabilitation) Program for COVID-19 Survivors Randomized Study.

BACKGROUND: Knowledge on physical activity recovery after COVID-19 survival is limited. The AFTER (App-Facilitated Tele-Rehabilitation) program for COVID-19 survivors randomized participants, following hospital discharge, to either education and unstructured physical activity or a telerehabilitation program. Step count data were collected as a secondary outcome, and we found no significant differences in total step count trajectories between groups at 6 weeks. Further step count data were not analyzed. OBJECTIVE: The purpose of this analysis was to examine step count trajectories and correlates among all participants (combined into a single group) across the 12-week study period. METHODS: Linear mixed models with random effects were used to model daily steps over the number of study days. Models with 0, 1, and 2 inflection points were considered, and the final model was selected based on the highest log-likelihood value. RESULTS: Participants included 44 adults (41 with available Fitbit [Fitbit LLC] data). Initially, step counts increased by an average of 930 (95% CI 547-1312; P<.001) steps per week, culminating in an average daily step count of 7658 (95% CI 6257-9059; P<.001) at the end of week 3. During the remaining 9 weeks of the study, weekly step counts increased by an average of 67 (95% CI -30 to 163; P<.001) steps per week, resulting in a final estimate of 8258 (95% CI 6933-9584; P<.001) steps. CONCLUSIONS: Participants showed a marked improvement in daily step counts during the first 3 weeks of the study, followed by more gradual improvement in the remaining 9 weeks. Physical activity data and step count recovery trajectories may be considered surrogates for physiological recovery, although further research is needed to examine this relationship. TRIAL REGISTRATION: ClinicalTrials.gov NCT04663945; https://tinyurl.com/2p969ced.

Rehabilitation Therapy Allocation and Changes in Physical Function Among Patients Hospitalized Due to COVID-19: A Retrospective Cohort Analysis.

OBJECTIVE: Limited staffing and initial transmission concerns have limited rehabilitation services during the COVID-19 pandemic. The purpose of this analysis was to determine the associations between Activity Measure for Post-Acute Care (AM-PAC) mobility categories and allocation of rehabilitation, and in-hospital AM-PAC score change and receipt of rehabilitation services for patients with COVID-19. METHODS: This was a retrospective cohort study of electronic health record data from 1 urban hospital, including adults with a COVID-19 diagnosis, admitted August 2020 to April 2021. Patients were stratified by level of medical care (intensive care unit [ICU] and floor). Therapy allocation (referral for rehabilitation, receipt of rehabilitation, and visit frequency) was the primary outcome; change in AM-PAC score was secondary. AM-PAC Basic Mobility categories (None [21-24], Minimum [18-21], Moderate [10-17], and Maximum [6-9]) were the main predictor variable. Primary analysis included logistic and linear regression, adjusted for covariates. RESULTS: A total of 1397 patients (ICU: n = 360; floor: n = 1037) were included. AM-PAC mobility category was associated with therapy allocation outcomes for floor but not patients in the ICU: the Moderate category had greater adjusted odds of referral (adjusted odds ratio [aOR] = 10.88; 95% CI = 5.71-21.91), receipt of at least 1 visit (aOR = 3.45; 95% CI = 1.51-8.55), and visit frequency (percentage mean difference) (aOR = 42.14; 95% CI = 12.45-79.67). The secondary outcome of AM-PAC score improvement was highest for patients in the ICU who were given at least 1 rehabilitation therapy visit (aOR = 5.31; 95% CI = 1.90-15.52). CONCLUSION: AM-PAC mobility categories were associated with rehabilitation allocation outcomes for floor patients. AM-PAC score improvement was highest among patients requiring ICU-level care with at least 1 rehabilitation therapy visit. IMPACT: Use of AM-PAC Basic Mobility categories may help improve decisions for rehabilitation therapy allocation among patients who do not require critical care, particularly during times of limited resources.

Association between Substance Misuse and Outcomes in Critically III Patients with Pneumonia.

Rationale: In patients with pneumonia requiring intensive care unit (ICU) admission, alcohol misuse is associated with increased mortality, but the relationship between other commonly misused substances and mortality is unknown. Objectives: We sought to establish whether alcohol misuse, cannabis misuse, opioid misuse, stimulant misuse, or misuse of more than one of these substances was associated with differences in mortality among ICU patients with pneumonia. Methods: This was a retrospective cohort study of hospitals participating in the Premier Healthcare Database between 2010 and 2017. Patients were included if they had a primary or secondary diagnosis of pneumonia and received antibiotics or antivirals within 1 day of admission. Substance misuse related to alcohol, cannabis, stimulants, and opioids, or more than one substance, were identified from the International Classification of Diseases (Ninth and Tenth Editions). The associations between substance misuse and in-hospital mortality were the primary outcomes of interest. Secondary outcomes included the measured associations between substance misuse disorders and mechanical ventilation, as well as vasopressor and continuous paralytic administration. Analyses were conducted with multivariable mixed-effects logistic regression modeling adjusting for age, comorbidities, and hospital characteristics. Results: A total of 167,095 ICU patients met inclusion criteria for pneumonia. Misuse of alcohol was present in 5.0%, cannabis misuse in 0.6%, opioid misuse in 1.5%, stimulant misuse in 0.6%, and misuse of more than one substance in 1.2%. No evidence of substance misuse was found in 91.1% of patients. In unadjusted analyses, alcohol misuse was associated with increased in-hospital mortality (odds ratio [OR], 1.12; 95% confidence interval [CI], 1.06-1.19), whereas opioid misuse was associated with decreased in-hospital mortality (OR, 0.46; 95% CI, 0.39-0.53) compared with no substance misuse. These findings persisted in adjusted analyses. Although cannabis, stimulant, and more than one substance misuse (a majority of which were alcohol in combination with another substance) were associated with lower odds for in-hospital mortality in unadjusted analyses, these relationships were not consistently present after adjustment. Conclusions: In this study of ICU patients hospitalized with severe pneumonia, substance misuse subtypes were associated with different effects on mortality. Although administrative data can provide epidemiologic insight regarding substance misuse and pneumonia outcomes, biases inherent to these data should be considered when interpreting results.